Lecture 2 Flashcards
(60 cards)
1
Q
What are the two layers of the skin and what are their purpose?
A
epithelial layer-
waterproof barrier
dermal layer- Supporting layer (if this layer affected by injury, this is where you would see more severe scarring)
2
Q
Components of the epithelial layer of skin
A
epithelial layer of skin
- keratinocytes (90%)
- barrier, melanocytes (pigmentation), immune cells
3
Q
Components of the dermal layer of skin
A
- Fibroblasts (matrix)
- Endothelial cells (vascular supply)
- Hair follicle cells
4
Q
What is the multi-step process of response to injury
A
- Clotting
- Vascular response
- Inflammation (drives wound repair)
- Scar formation
- Epithelial healing
- Contraction
- Scar remodelling
5
Q
What are the two things to consider when treating burn injuries?
A
- Amount of SA covered
2. Depth of burn
6
Q
What is the recommended treatment for total body SA burns?
A
Donor site availability (inc. SA burn = dec. donor site avail.)
7
Q
What is the recommended treatment for depth burns?
A
Intrinsic repair capacity
8
Q
What are the 4 types of burns?
A
- Epithelial burns
- Partial thickness burn
- Deep dermal burn
- Full thickness burn
9
Q
What are the treatments for the 4 types of burns?
A
- Epithelial burns = conservative
- Partial thickness burn = dermabrade + CEA
- Deep dermal burn = mesh graft + CEA
- Full thickness burn = Integra + mesh graft + CEA
10
Q
Skin grafts - facts
A
- Graft taken from patients healthy site
- Skin is meshed to cover large wound
- donor site morbidity
- limited size (1:3 expansion common, max 1:5)
- mesh pattern of healed skin
11
Q
What is a xenograft skin sources?
A
- graft from animals, typically pigs, cats, rabbit and mice
- usually not cultured
- vigorous rejection, therefore limited to temporary biological dressing
12
Q
What are allografts skin sources?
A
- graft from same species (humans)
- typically cadaveric or neonatal donors
- Eventual rejection due to HLA-DR antigens
- Immunosuppressive therapy must be given to prevent early rejection
- risk of cross contamination
13
Q
What are cultured epithelial autograft (CEA) sheets?
A
- cultures using a large, full-thickness biopsy
- cultured as confluent sheets in the lab
- Generally 3-10 cell layers thick
- Clipped to a petrolatum gauze backing
- available 3-5 weeks after initial biopsy
Difficulties = fragility and inability to take
14
Q
What are the cell types and therapeutic approaches to burns?
A
- keratinocytes = epithelial cover
- fibroblasts = dermal matrix
- melanocytes
- endothelial cells = revascularisation
15
Q
What is the scar risk of burn that has 10 days to heal?
A
4%
16
Q
What is the scar risk of a burn that has over 21 days to heal?
A
78%
17
Q
What is an example of non-cultured skin cell based therapy?
A
Cell spray
18
Q
Cell spray skin therapy
A
- expanding cell no.
- greater coverage of cells from small biopsy
- still involves skin biopsy
- spray @ smaller density –> seed larger area
- promotes healing over larger area quicker
19
Q
What are the physical characteristics of ECM & dermal scaffold use?
A
- strength
- stress
20
Q
What are the biological characteristics of ECM & dermal scaffold use?
A
- secreted factors
- glycosylation/sugars
21
Q
Matrices - skin burn therapy
A
- collagen based (or elastin/collagen - matriderm)
- deep & extensive burns = rapid replacement of dermal template to enhave recovery
- limited by angiogenesis into new template
- matirces = avascular
22
Q
Laser scar amelioration
A
= adjunct therapies
- create micro-holes in skin
- creating micro-damage and allowing it to re-heal
- OCT imaging - measure vascularisation
23
Q
First 48 hours of a burn?
A
Stabilise, control and plan;
ABC, fluid resuscitation, escarotomies, infection control
24
Q
Initimate relationship between blood and ____ supply
A
nerve
25
skin turnover
6 - 8 weeks
26
Elements needed for wound healing
source of cells capable of differentiation; framework for cell migration; 3D spatial information of the wound area; feedback mechanisms to guide self organisation
27
Fundamental to survival of burn injuries
Time to healing
28
Integrins
Essential for would healing-graft take and enable:/ cell migration; cell proliferation; cell differentiation; cell stratification
29
Cell migration and proliferation
Predominantly occurs along with would bed covering
30
State of integrins expressed by epidermal cells
Pre-confluent state
31
Yorkshire pig model to study effects of sprayed keratinocytes on wound healing
animal model to study application of cells by spray; achieve normal and functional dermal epidermal junction; * melanocyte repopulation
32
Cytokeratin 9 (CK9+ive)
Useful marker of glabrous skin and is used to confirm CEA 'take'
33
Trans-epidermal water loss study
inverse relationship between extent of wound healing and water loss; measured via SEC
34
Correlates with loss of water from surface of a wound
wound epithelialisation; epithelial maturation
35
Surface electrical capacitance (SEC)
Measurement of trans-epidermal water loss
36
Role and timing of epidermal repair and recover on AP-1 inhibition and programmed cell death
AP-1 family transcription factors; c-Jun
37
AP-1 transcription factors
* involved in proliferation, transformation, inflammation and cell death
38
c-Jun
member of AP-1 family transcription factors; activates cell death pathways and inflammation
39
Impact of first aid
reduced length of stay 21%; reduced rate of infection 56%;* reduced need for surgery 52%
40
Alteration in structure of scaffolds at the ________ affects wound healing
* micron-level
41
Integra and ReCell
In situ guided tissue regeneration of both dermis and epidermis/ integra dermal template seeded with cell suspension harvested from the dermal epidermal junction;* epidermal cells migrate through the integrated to develop an intact epidermal layer
42
Future of cell delivery
with biologically active complexes for tissue salvage and cell adhesion; static architecture influence cell behaviour; an interactive composite cell scaffold with external trigger potential; potential for future drug delivery methods - safest method is through the skin
43
Where are the cells for spray on skin derived from
Dermal-epidermal junction
44
Which cells are more likely to be successful (skin)
Immature or mature?
Immature
45
In damaged tissue, the dead/non salvageable zone is called the ___________
Zone of coagulation
46
Describe briefly what happens to sensory functionality, in an area of skin that has been burned - What happens in non-injured skin areas
Sensory functionality is reduced where you have been burned. Nerve density decreases in proportion to the total burn surface injury - i.e. nerve density even decreases in body areas that have not been injured.
47
How long did it take to make CEAs
3-5 weeks initially, later 10 days
48
How long does it take to make a cell suspension
~5 days initially, now only around 20 min
49
How thick are CEAs
3-10 cell layers
50
What determines the characteristics of harvested skin
The characteristics of the original site
51
What is the advantage of delivering cells as a suspension, rather than a sheet
Suspension more active- less secondary problems, like blistering
52
What is the relationship between extent of wound healing and water loss
Inverse relationship
53
What structural characteristic of Integra is important
Pore size- if too big/small, cells may grow in a disordered fashion; Architecture matters
54
When are cell suspensions given to the patient
Between days 2-5
55
Why can't cell suspensions be given too early
Patient not stabilised yet- might "over-do" or "under-do" treatment
56
What does the skin do after inflammation response to injury?
Creating inflammatory response-
Epithelial layer of skin can’t regenerate until it has filled its surface to close over.
Requires granulation tissue (temp dermis)
Epithelial cells migrate over
Once closed, limited chance of infection
57
What are the the two drivers of burn injury?
TBSA- donor site availability
Depth- intrinsic repair capacity
58
What is Epidermolysid bullosa?
Epidermolysis bullosa
(EB) is a group of genetic conditions that result in easy blistering of the skin and mucous
membranes. Blisters occur with minor trauma or friction and are painful. Its severity can range from mild to fatal. Those with mild cases may not develop symptoms until they start to crawl or walk
59
What mutation causes epidermolysis bullosa
LAMB3 mutation
60
How would you treat Epidermolysis bullosa and how is this therapy effective?
Use viral vector with unmutated LAMB3 and introduce into patients own epithelial cells and put back into body.
Patients own epithelial break off. Unmutated LAMB3 has a survival advantage and is able to attach to dermis underneath. Really good regenerative capacity.
